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A study about the impaired mitochondrial membrane potential and nuclear body formation, and their relationship with the induction of cell senescence and cell death

Research Project

Project/Area Number 17590159
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionNAGOYA UNIVERSITY

Principal Investigator

NISHIO Koji  NAGOYA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, Research associate, 大学院医学系研究科, 助手 (60252235)

Co-Investigator(Kenkyū-buntansha) INOUE Akira  OSAKA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, Associate Professor, 大学院医学研究科, 助教授 (50109857)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordstumor cells / protein phosphorylation / nuclear body / PML / RBM10 / tumor suppressor gene / apoptosis / casein kinase / ヌクレオボディ / 老化細胞 / 核内輸送機能 / S1-1 / 老化シグナル
Research Abstract

With fluorescently labeled S1-1 isoform specific antibodies and PML isoform specific antibodies, we examined the nuclear bodies of cultured human normal cells (TIG3S), HeLa cells, various normal rat tissues, and various human tumor tissues with the corresponding normal tissues. In young TIG3S cells, S1-1 nuclear bodies were rarely observed, but PML2, 4, 5, 6 nuclear bodies were observed significantly. Furthermore, co-localization of S1-1 and PML6 nuclear bodies was confirmed. In HeLa cells, S1-1 nuclear bodies were hardly observed. In addition, the remarkable cytoplasmic localization of S1-1 and of PML protein, significant nuclear bodies of PML2 and PML6, and rare nuclear bodies of PML4 and PML5 were observed. We confirmed the rare S1-1 nuclear bodies in dividing young TIG3S and HeLa cells. In addition, the S1-1p110 protein levels of young TIG3S and HeLa cells were very low, on the contrary, the S1-1p130 protein was at very high levels. Furthermore, the S1-1p130 level of HeLa cells was 3-fold higher than TIG3S cells. PML and S1-1(RBM10) have many phosphorylation sites by CK2 and PKC, and HeLa cells have significantly higher activity of CK2 than normal cells. Thereby, the PML isoforms which are phosphorylated (S517 of PML) by CK2, degrade in the proteasomes. However, S1-1p130 (RBM10 variant-1) was very stable even in HeLa cells. HeLa and TIG3S cells, which administered with PKC or CK2 inhibitor, significantly developed the S1-1 nuclear bodies. This suggests that the assembly of S1-1 nuclear bodies was suppressed through their phosphorylation by CK2 in the actively dividing cells. In the presence of PKC or CK2 inhibitor, but not CDK2 inhibitor, cell division of HeLa or TIG3S cells was strongly impaired, and the drugs promoted cell death. Our results suggest that S1-1 and PML nuclear bodies regulate the cell growth and promote the cell death pathway

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (6 results)

All 2005

All Journal Article (6 results)

  • [Journal Article] Senescence-associated alterations of cytoskeleton : extraordinary overproduction of vimentin that anchors cytoplasmic p53 in senescent human fibroblasts.2005

    • Author(s)
      Koji Nishio
    • Journal Title

      Histochemistry & Cell Biology 123

      Pages: 263-273

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Characterization of the Differential expression of Uncoupling Protein 2 and Ros production in Differentiated Mouse macrophage-cells (Mm1) and the progenitor cells (M1).2005

    • Author(s)
      Koji Nishio
    • Journal Title

      Journal of Molecular Histology 36

      Pages: 35-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Association of hnRNP S1 proteins with vimentin intermediate filaments in migrating cells.2005

    • Author(s)
      Akira Inoue
    • Journal Title

      Journal of Cell Science 118

      Pages: 2303-2311

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Senescence-associated alterations of cytoskeleton : extraordinary overproduction of vimentin that anchors cytoplasmic p53 in senescent human fibroblasts.2005

    • Author(s)
      Koji Nishio
    • Journal Title

      Histochemistry & Cell Biology 123

      Pages: 263-273

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Characterization of the Differential expression of Uncoupling Protein 2 and Ros production in Differentiated Mouse macrophage-cells (Mm1) and the progenitor cells(M1).2005

    • Author(s)
      Koji Nishio
    • Journal Title

      Journal of Molecular Histology 36

      Pages: 35-44

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of hnRNP S1 proteins with vimentin intermediate filaments in migrating cells.2005

    • Author(s)
      akira Inoue
    • Journal Title

      Journal of Cell Science 118

      Pages: 2303-2311

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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